Researcher's Profile

Our laboratory has continuously been trying to clarify the pathophysiology of lifestyle diseases and to discover effective countermeasures to restore health. Our recent project has centered around the mechanisms of hypertension and organ damage induced by excess salt. We have found that a small GTPase, Rac1, activates the mineralocorticoid receptor (MR) which regulates the internal sodium balance and blood pressure, independently from aldosterone. We have also shown that an aberrant Rac1-MR pathway is involved in the development of salt-induced hypertension. Activation of hypothalamic-renal sympathetic nervous system is also participated in obesity-induced salt-sensitive hypertension, through the activation of β-adrenergic-NCC pathway, which increases the reabsorption of sodium in the renal tubules. Accordingly, an epigenetic mechanism plays an important role in the prenatal programmed salt-sensitive hypertension evoked by hypothalamic-renal sympathetic overactivity (DOHaD hypothesis). Recently, our group found that salt-induced activation of vascular Wnt5a-RhoA pathway under the anti-aging factor Klotho deficiency is involved in aging-associated salt-sensitive hypertension. Thus, the salt-sensitivity of blood pressure in individuals is modulated by environmental factors in life; infancy to the elderly. Our goal is to systematically elucidate the mechanism for the epigenetic regulation of gene transcription in salt-induced hypertension. Moreover, epigenetics is known to be involved in the progression of organ damage, and our intriguing mission is to elucidate the mechanism and apply this knowledge to the development of new therapies.